DESCRIPTION: Periodontitis is the major cause of teeth motility and loss. Twenty percent of adult Americans suffer severe periodontitis, resulting in destruction of the supporting structures of teeth, including the alveolar bone. Periodontal surgery can slow the progression of the disease, but is costly, limited by contraindications, often requires repeated treatment and does not regenerate lost periodontal structures. To that end, several regenerative modalities have been employed. Of particular interest has been the use of biologicals, such as bone morphogenetic proteins and angio-stimulatory growth factors (e.g., bFGF). Unfortunately, these stimulators undergo proteolysis, and cannot be readily maintained in treatment sites at therapeutic levels. Here, we propose to test the regenerative capabilities of SBD.4-a novel stable, non-proteinaceous molecule isolated from a medicinal plant, strongly stimulating angiogenesis, fibroblast and osteoblast growth and collagen synthesis-the activities needed for periodontal regeneration. We will further characterize this new compound and will test it in the murine calvarial bone regeneration model, which is particularly suitable for pilot testing of potential anti-periodontitis therapies. Targeted endpoint will be increased bone regeneration by at least 30% as measured by micro-computerized tomography and histomorphometry. If successful, this project will result in a preclinical drug candidate for treatment of periodontal disease.